Small volume liquid manipulation, method, apparatus and process

ABSTRACT

An apparatus, a method and a process to achieve manipulation of particles and/or solutions through the use of electrokinetic properties are disclosed. The manipulation is performed using a disposable device positioned on top of a stage for purposes of powering the electrodes. The fluidic solution is brought into contact with the active part of the device and then manipulated.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit under 35 U.S.C. Section 119(e) ofco-pending and commonly-assigned U.S. Provisional Patent ApplicationSer. No. 60/917,796 filed on May 14, 2007, by Igor Mezic et al.,entitled “SMALL VOLUME LIQUID MANIPULATION, METHOD, APPARATUS, ANDPROCESS,” attorneys' docket number 30794.235-US-P1 (2006-673-1), whichapplication is incorporated by reference herein.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT

This invention was made with Government support under Grant No.DMS-0507256 awarded by the NSF. The Government has certain rights inthis invention.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates in general to the field of manipulatingfluid flow and/or particle motivating force and is related toseparation, concentration, transport, reaction and mixing apparatus,method and process. More particularly, the present invention relates toimproved manipulation by bringing the present invention in contact withthe solution. Moreover, the invention can be embedded into existingliquid-containing vessels such as well-plates and microarrays.

2. Description of the Related Art

(Note: This application references a number of different publications asindicated throughout the specification by one or more reference numberswithin brackets, e.g., [x]. A list of these different publicationsordered according to these reference numbers can be found below in thesection entitled “References.” Each of these publications isincorporated by reference herein.)

Devices using electrokinetic properties (electrophoresis,dielectrophoresis, electroosmosis and electrothermal convection) havebeen used to manipulate fluids and particles.

Electrophoresis is a technique for manipulating components of a mixtureof charged molecules (proteins, DNAs, or RNAs) in an electric fieldwithin a gel or other support. Under AC electric field, unchargedparticles suspended in a dielectric media can be polarized and furthermanipulated. If the field is spatially inhomogeneous, it exerts a netforce on the polarized particle known as dielectrophoretic (DEP) force[1]. This force depends upon the temporal frequency and spatialconfiguration of the field as well as on the dielectric properties ofboth the medium and the particles. Single frequency electric fields canbe used to transport and separate particles.

Fluid motion can also be induced by applying an electric field onto asolution. The force driving the fluid thus originates in the bulk(buoyancy, electrothermal effect) or at the interface between the fluidand the device containing the fluid (electroosmosis).

The buoyancy generates a flow because of a density gradient. It can beproduced by internal or external heating. An electric field is oftenused as internal energy source. Applied to a solution, part of theelectric energy dissipates in the fluid by Joule effect and locallyheats the fluid. Furthermore, local heating creates gradients ofconductivity and permittivity. The fluid can then move under theinfluence of an electrothermal flow [2, 3, 4].

Under certain conditions (material properties, conductivity andpermeability of the fluid and the device containing the fluid), ionlayers develop at the fluid-surface interface due to chemicalassociations or dissociations and physical adsorption on or desorptionfrom the solid surface. Ion layers can also be generated at the surfaceof electrodes where a potential is externally imposed. Appling anelectric field with a tangential component to the layers moves the ionswhich carry the fluid along by viscous force. This process produces abulk flow [2, 3, 4].

Coupled with an electrohydrodynamic flow, several electrode geometrieshave been designed as a tool to manipulate fluids and particles.Interdigitated castellated electrodes are, for instance, designed totrap and separate particles [5, 6]. Polynomial electrodes [7], planarelectrodes [8, 9], quadripolar electrodes [27] or more complexgeometries [10] have also been proposed.

Micro Technology Applied to Biological Problems

Massively parallel hybridization [11-13] improves the way manybiological and medical analyses are performed both in research andclinical applications, but there is still a lack of an efficientmultipurpose device. As sample volumes used in massive parallel systemsbecome smaller and smaller (micro- to nanoliter or even smaller) it ismore challenging to manipulate the fluids since the fluid viscositydominates any convection. Multiple reports have shown that micromixing,transport or concentration improves hybridization reaction[14-16,17,18]. Micromixing can be achieved by ultrasonic agitation (thenucleation of bubbles creates small jets that enhance the mixing) [19]or by vortexing or agitating the solution and creating convection [20].Micromixing can also be produced by surface wave generation [21] forinstance.

What is needed then are improved methods, processes and generalapparatus to efficiently and accurately mix, separate, concentrate, andtransport small volume of fluids with or without particles (e.g., atoms,molecules, cells in biological and chemical assays) using combined fluidflow and/or electrokinetic methods. The present invention satisfies thatneed.

SUMMARY OF THE INVENTION

The present invention discloses an apparatus, a method and a process toachieve manipulation of particles and/or solutions in a container. Theinvention uses electrokinetic properties. The manipulation is performedby bringing the fluidic solution into contact with the active part ofthe device. For the purpose of this document, a “vessel” will denotespecifically either a microtiter plate (microplate or well-plate) wellor more generally any volume containing liquid solution. The inventionincludes a process where one or more vessels with built in electrodes(made of any applicable material) are filled with one or more fluids orone or more fluids and one or more types of particles for the purpose ofmanipulating fluid(s) and/or particles. The manipulations can includeconcentration, separation, transport or mixing.

A device composed of two parts comprising vessels containing electrodescapable of inducing electrokinetic (including electroosmotic andelectrothermal) fluid flow inside vessels (including microplates orwell-plates) and a connecting plate (the vessels bloc being a separateentity from the connecting plate).The electrodes contacts or pads areaccessible from outside the vessels. The electrodes are energizedthrough the connecting plate by bringing into contact the electrodescontacts or pads with the connecting plate. The electrodes are builtinto the vessel, itself. The device can be used for general manipulationof fluids and particles inside the vessel, including concentration,separation, transport or mixing. The device is tunable, so that byapplying different DC and/or AC voltages, different flow effects can beinduced and adapted to efficiently manipulate the fluids and particlescontained inside the vessel. The device can perform one or more particlemanipulation operations.

A method where more than one frequency of AC field is used to inducefluid flows sequentially in time or simultaneously to induce fluid flowand electromagnetic field for the purpose of manipulating particles(including concentration, separation, transport or mixing of theparticles). The flow and electromagnetic field can be applied byelectrodes built into the device (thus being an integral part of thedevice) or applied externally. A device for manipulating fluidicsolutions in accordance with the present invention comprises a vesselfor containing a fluidic solution, and a plurality of electrodes,coupled to the vessel, the plurality of electrodes being arranged in anarray and each applying an electric field to the fluidic solution,wherein the plurality of electrodes manipulate at least one of a flow ofthe fluidic solution and a separation of particles in the fluidicsolution, the manipulation using electrokinetic properties resultingfrom the applied electric fields, wherein the fluidic solution comprisesa total volume of fluid on the order of microliters.

Such a device further optionally comprises the electrokinetic propertyis at least one of electrothermal convection and electroosmosis, atleast a first electrode in the plurality of electrodes being made from afirst material and at least a second electrode in the plurality ofelectrodes being made from a second material, the array being a periodicarray, each electrode in the periodic array being controlledindependently, at least a first electrode in the plurality of electrodeshaving a first shape and at least a second electrode in the plurality ofelectrodes having a second shape, and the electric field inducing atime-dependent electrohydrodynamic fluid flow.

A method in accordance with the present invention comprises forming atleast one recurrent circulating fluid flow within the fluid, introducingat least one particle motivating force to the fluid having the recurrentcirculating fluid flow, and manipulating the at least one particlemotivating force using electrokinetic properties, the particlemotivating force comprising at least applied electric fields, whereinthe fluidic solution comprises a total volume of fluid on the order ofmicroliters.

Such a method further optionally comprises at least one particlemotivating force directionally interacting with the at least onerecurrent circulating fluid flow in a tangential orientation relative tothe recurrent circulating fluid flow, the at least one particlemotivating force directionally interacting in a tangential orientationat a periphery of the at least one recurrent circulating fluid flow,collecting the particles, and applying a time-dependentelectrohydrodynamic fluid flow.

Another device in accordance with the present invention comprises avessel for containing the fluid to be mixed, a plurality of electrodes,inside the vessel, and a plurality of connectors, coupled to theplurality of electrodes, the plurality of connectors being electricallycoupled to a plurality of applied electric fields, wherein the pluralityof electric fields electrically excite the electrodes thereby creating aflow within the fluid.

Such a device further optionally comprises the plurality of electricfields generating at least one of electrothermal convection andelectroosmosis within the fluid, at least a first electrode in theplurality of electrodes being made from a first material and at least asecond electrode in the plurality of electrodes being made from a secondmaterial, the plurality of electrodes being arranged in a periodicarray, each electrode in the periodic array being controlledindependently, at least a first electrode in the plurality of electrodeshaving a first shape and at least a second electrode in the plurality ofelectrodes having a second shape, and the electric field inducing atime-dependent electrohydrodynamic fluid flow.

BRIEF DESCRIPTION OF THE DRAWINGS

Referring now to the drawings in which like reference numbers representcorresponding parts throughout:

FIG. 1 illustrates an example of the arrangement of the electrode arraysinside a vessel. The electrodes connectors are on the bottom of thevessel.

FIGS. 2( a) through 2(c) illustrate examples of the vessels (withembedded electrodes) arrangement to form a wells plate. FIG. 2( a) showsthe vessels on top of the holding plate with the electrodes connectorson the backside on the plate. FIG. 2( b) shows the vessels inserted intothe holding plate with the electrodes connectors on the bottom of thevessels. FIG. 2( c) shows the electrodes directly inserted into theholding plate with the electrodes connectors on the backside of theplate.

FIG. 3 illustrates an example of a connecting plate. In this example,each row can be controlled separately. The electrode pads (shown indetail in FIG. 4) are wired to link the electrode pads to an externalcontroller. The wires are drawn on the backside of the plate in thisexample but can by on any side of the plate.

FIGS. 4( a) and 4(b) illustrates an example of a vessel with electrodesfrom a side view (a) and a connection on the electrodes array (b). Theconnectors of the array have conic shape with flexible conductive flapsdesigned to enable reliable contacts.

FIG. 5 is a drawing of a vessel with embedded electrodes with astreamline of the flow once the electrodes are energized.

FIG. 6 is a block diagram that illustrates examples of the arrangementof the electrode inside a vessel. FIG. 6( a) is a drawing of alignedcylindrical electrodes, FIG. 6( b) is a drawing of cylindricalelectrodes arranged in staggered row, FIG. 6( c) is a drawing ofcylindrical electrodes with different length arranged in staggered row,FIG. 6( d) is a drawing of cylindrical and circular electrodes, and FIG.6( e) is a drawing of curved cylindrical electrodes. The electrodes canalso be mounted on the plate without a container around them.

FIG. 7 is a graph that shows the velocity field in the plane orthogonalto the electrodes for the electrode configuration shown in FIG. 6( a).The velocity field is measured par Particle Image Velocimetry at midheight of a cell measuring 570 μm high, 2 mm wide and 2 mm long. Thefluidic solution was water with conductivity σ=0.6 S·m⁻¹ seeded with0.71 μm fluorescent particles. The signal applied was 530V·cm⁻¹ at 700KHz.

FIG. 8 is a process chart in accordance with the present invention.

DETAILED DESCRIPTION OF THE INVENTION

In the following description of the preferred embodiment, reference ismade to the accompanying drawings which form a part hereof, and in whichis shown by way of illustration a specific embodiment in which theinvention may be practiced. It is to be understood that otherembodiments may be utilized and structural changes may be made withoutdeparting from the scope of the present invention.

Overview

The impact of the manipulation of fluids and/or particles induced byelectric fields is described theoretically and experimentally herein. Bymeans of a microfluidic device comprising a periodic array ofmicroelectrodes, fluid(s) and/or particles manipulations are shownincluding concentration, separation, transport or mixing usingelectrokinetic properties. The theoretically predicted dynamicalphenomena are demonstrated experimentally.

This invention could be used, for example, to improve the mixing ofmicroliter or nanoliter volume protein solutions analyzed in highthroughput screening assays. Electrokinetic micromixing improves thetime and reliability for protein expression by rapidly homogenizing thesmall volume solution. Current methods require extensive.human orrobotic operations and generally lack the required sensitivity to meetreliability testing standards. Other possible applications could be theseparation and detection of small populations of pre-cancerous cellsfrom body fluids (blood, sputum, urine) or the concentration of DNAparticles inside a Polymerase Chain Reaction (PCR) apparatus forimproved DNA detection.

Technical Description

The present invention discloses an apparatus, a method and a process toachieve manipulation of particles and/or solution in micro- to nanolitervolumes. Volumes on the order of microliters means that the total volumeof the fluid is less than one milliliter, but the device can be usedwith total volumes greater than one milliliter if desired. The device ofthis invention uses electrokinetic properties. The manipulation isperformed by positioning vessels onto the electrodes arrays for purposeof powering the electrodes, bringing the fluidic solution consideredinto contact with the active part of the device in the vessels andapplying precise and carefully chosen electric fields combinations. Thepurpose of the active part of the device is to manipulate the flowand/or particles using an electric field.

Electric fields induce a force on charged particles in solutions, movingthe particles towards either the cathode or the anode depending on thesign of the charged particles [22]. Such a particle motion in liquidphase is called electrophoresis. If the particle is uncharged, applyingAC-electric field to the medium containing the particles creates adipole on the particles. The orientation of the dipole depends on theconductivity and permittivity of both the particles and the medium. Fordielectric particles, the expression of the time average force is givenby

F _(DEP)

=2πα³ε_(m) Re[K(ω)]∇|E| ²

where E is the rms electric field, α is the particle radius, ω is theangular field frequency, and Re[z] indicates the real part of thecomplex number z. The factor K(ω) is a measure of the effectivepolarizability of the particle, known as the Clausius-Mossotti factor,given by

K(ω)=(ε*_(p)−ε*_(m))/(ε*_(p)+2ε*_(m))

where ε*_(p) and ε*_(m) are the complex permittivities of the particleand the medium, respectively. The complex permittivity is defined asε*=ε−i(σ/ω), where i=√{square root over (−1)}, ε is the permittivity,and σ is the conductivity.

The particles submitted to a non uniform electric field will move towardor away from the high electric field region depending on the sign ofRe[K(ω)]. The motion of the particles is called dielectrophoresis.

Electrophoresis and dielectrophoresis are two major subjects in particleseparation and transport. For separation purposes, let's consider acommon case where two types of particles are present in the solution.

Separation occurs when there is a frequency ω_(s) for which Re[K(ω)]takes a different sign for each particle type. For particles havingclose properties ω_(s) might be impossible to apply experimentally. Inthat case [23] have shown that two superposed AC-electric fields withtwo different frequencies ω_(s1) and ω_(s2) enables the particleseparation. ω_(s1) and ω_(s2) being two frequencies for which eachparticle type has a Clausius-Mossotti factor of opposite sign.

Consider a simple but commonly used configuration of an electrode arrayfor which a closed-form solution of the electric field and the DEP forcewas derived in [23]. It is comprised of a periodic array of longparallel micro-electrodes. Each electrode submitted to an AC-electricfield with a defined phase difference with their neighbors willsimultaneously separate and transport the particles through the system[23]. The process is named traveling wave dielectrophoresis.

Electric fields induce fluid and/or particle motions through severalelectro-hydrodynamic, electrophoretic or dielectrophoretic effects.Among all the effects the flow is submitted to, the most important inmicroelectrode devices are electrothermal convection and electroosmosis.The former appears to be due to a non-uniform Joule heating of the fluidwhich leads to gradients of its permittivity and conductivity. Theapplied electric fields acting on the permittivity and conductivitygradients generate electrical body forces that induce the flow [13]. Thelatter is caused by electrical stresses in the diffuse double layer ofcharges accumulated above the electrodes (AC-electroosmosis) [14] or atthe walls (electroosmosis) [24]. These stresses result in a rapidlyvarying fluid velocity profile in the diffuse double layer, going fromzero at the wall to a finite value just outside the double layer.Whether electrothermal or AC-electroosmotic flows dominate the motion offluid in the device depends mainly on the frequency of the appliedelectric field and the conductivity of the medium, AC-electroosmosisbeing dominant at a frequency range several orders of magnitude belowthe charge relaxation frequency (ω_(c)≈σ/ε) for low conductivity media.

If the applied frequency is chosen carefully, the induced effects willmost affect the fluid flow and produce efficient mixing, for instance.Using multifrequency electric field signals [8] will, most of the time,improve even more the flow manipulation.

Dielectrophoresis and fluid flow precisely combined make possible themanipulation of submicron particles. For a careful choice of the appliedfrequency, the electro- hydrodynamically induced fluid flows will have aminimal effect but will be determinant in the DEP manipulation and/orseparation of submicron particles. It has been shown that the induceddynamical properties can be creatively used as a mechanism to controlmicro or submicron particles. Experiments and numerical simulations ofthe coupled electro-thermo-hydrodynamic problem in devices withinterdigitated arrays of electrodes [12, 13, 14] or electrode poles [26]show that both electrothermal and AC-electroosmotic flows consist ofconvective rolls centered at the electrode edges and provide goodestimates for their strength and frequency dependence. Near theelectrodes, the fluid velocity u₀ ranges from 1 to 1000 μm·s⁻¹ decayingexponentially with the transversal distance to the electrodes.

In a device of characteristic length d=150 μm, fluid viscosity v=10⁻⁶m²s⁻¹ , conductivity δ=0.6 S·m⁻¹ with AC-electric field of 530V/cm, themaximum flow velocity is measured to be 150 μm·s⁻¹ [FIG. 7].

The electric field induced heating inside the solution induces buoyancyflow effects. These are caused by gravity acting on nonhomogeneities indensities inside the liquid solution to induce flow. These are possiblyused in the device in conjunction with electrokinetic/electrothermaleffects to provide mixing, concentration, separation and transporteffects.

The invention apparatus contains electrodes capable of producing any ofthe physical properties described in the sections above. The device iscapable of inducing electrokinetic (including electroosmotic andelectrothermal) fluid flow inside vessels (including microplates orwell-plates and microarray hybridization solutions). The electrodearrays are designed to fit microliter size (or smaller) vessels as wellas microliter (or smaller) droplets. The electrodes are generally micronsized wires shaped like [FIG. 6-FIG. 7]. For micromixing, one mightprefer pole electrodes since the fluid can flow between the electrodes,for instance [FIG. 7]. The electrode array pitch is optimized dependingon the application and the electric field strength.

For parallel applications like well-plates or microarrays, the devicecan comprise sets of individually tunable or not tunable electrodearrays as shown [FIG. 2].

The fluidic solution is either put in the vessels then the vessels,vessels array or vessels plate is inserted in the connecting plate orthe vessels, vessels array or vessels plate is first inserted in theconnecting plate then the vessels are filled. The vessels, vessels arrayor vessels plate can be disposable. The device can be used for generalmanipulation of fluids and particles inside the vessel, includingconcentration, separation, transport or mixing. The device is tunable,so that by applying different DC and/or AC voltages, different floweffects can be induced and adapted to efficiently manipulate fluids andparticles contained inside the vessel. The device can perform one ormore particle manipulation operations. The device is flexible. It can betuned and adapted to a variety of configurations depending on theapplication.

The process of this invention is to bring the fluid and/or particlesolution in contact with the electrodes and to bring the electrodes incontact with the connecting plate. The electrodes can be embedded withinthe vessel or plate. Bringing the solution in contact with theelectrodes and applying the appropriate electric field will enablemanipulation of the fluidic solution.

References

The following references are incorporated by reference herein:

1. H. A. Pohl, Dielectrophoresis (Cambridge University Press, 1978).

2. N. G. Green, A. Ramos, A. Gonzalez, H. Morgan, A. Castellanos, Phys.Rev. E 61, 4011 (2000).

3. A. Ramos, H. Morgan, N. G. Green, A. Castellanos, J. Phys. D: Appl.Phys. 31, 2338 (1998).

4. N. G. Green, A. Ramos, A. Gonzalez, H. Morgan, A. Castellanos, Phys.Rev. E 66, 026305 (2002).

5. PETHIG R, HUANG Y, WANG X B, BURT J P H, “POSITIVE AND NEGATIVEDIELECTROPHORETIC COLLECTION OF COLLOIDAL PARTICLES USING INTERDIGITATEDCASTELLATED MICROELECTRODES,” Journal of Physics D-Applied Physics 25(5): 881-888 MAY 14, 1992.

6. Arnold W M, Franich N R, Cell isolation and growth in electric-fielddefined micro-wells, APPLIED PHYSICS 6 (3): 371-374 JUNE 2006

7. H. Morgan, M. P. Hughes, and N. G. Green, “Separation of submicronbioparticles by dielectrophoresis,” Biophysical Journal 77 (1999)516-525.

8. I. Tuval, I. Mezic, F. Bottausci, Y. T. Zhang, N. C MacDonald and O.Piro, Control of particles in microelectrode devices, Physical ReviewLetters 95(23) December 2005

9. J. Suehiro, and R. Pethig, “The dielectrophoretic movement andpositioning of a biological cell using a three-dimensional gridelectrode system,” Journal of Physics D: Applied Physics 31 (1998)3298-3305.

10. T. Müller, G. Gradl, S. Howitz, S. Shirley, T. Schnell, and G. Fuhr,A 3-D microelectrode system for handling and caging single cells andparticles, Biosensors & Bioelectronics 14 (1999) 247-256.

11. Marshall A and Hodgson J 1998 DNA chips: an array of possibilitiesNat. Biotechnol. 16 27.

12. Southern E, Mir K and Shchepinov M 1999 Molecular interactions onmicroarrays Nat. Genet. 21 (Suppl.) 5-9.

13. Xiang C C and Chen Y 2000 Biotechnol. Adv. 18 35-46.

14. Liu J, Williams B A, Gwirtz R M, Wold B J, Quake S, ANGEWANDTECHEMIE-INTERNATIONAL EDITION 45 (22): 3618-3623 2006.

15. Yuen P K, Li G S, Bao Y J, Muller U R, Microfluidic devices forfluidic circulation and mixing improve hybridization signal intensity onDNA arrays LAB ON A CHIP 3 (1): 46-50 2003.

16. Sasakura Y, Kanda K, Fukuzono S, Microarray techniques for morerapid protein quantification: Use of single spot multiplex analysis anda vibration reaction unit, ANALYTICA CHIMICA ACTA 564 (1): 53-58 MAR.30, 2006.

17. F Fixe, H M Branz, N Louro, V Chul, D M F Prazeres and J P Conde,Electric-field assisted immobilization and hybridization of DNAoligomers on thin-film microchips, Nanotechnology 16 (2005) 2061-2071.

18. Sigurdson M, Wang D Z, Meinhart C D, Electrothermal stirring forheterogeneous immunoassays, LAB ON A CHIP 5 (12): 1366-1373 2005.

19. Robin H. Liu, Ralf Lenigk, Piotr Grodzinski, Acoustic micromixer forenhancement of DNA biochip systems J. Microlith., Microfab., Microsyst.,Vol. 2 No. 3, July 2003 179.

20. J Vanderhoeven, K, Pappaert, B, Dutta, P. V, Hummelen and G. DesmetDNA Microarray Enhancement Using a Continuously and DiscontinuouslyRotating Microchamber, Anal. Chem. 2005, 77, 4474-4480.

21. M. Hartmann a, A. Toeglb, R. Kirchner b, M. F. Templin a, T. O.Joos, Increasing robustness and sensitivity of protein microarraysthrough microagitation and automation Analytica Chimica Acta 564 (2006)66-73.

22. D. Li, electrokinetics in microfluidics, Elsevier Academic Boston2004.

23. D. E. Chang, S. Loire, I. Mezic, J. Phys. D: Appl. Phys. 36, 3073(2003).

24. Yang R J, Fu L M, Lin Y C, Electroosmotic flow in microchannels,JOURNAL OF COLLOID AND INTERFACE SCIENCE 239 (1): 98-105 JUL. 1, 2001.

26. Squires T M, Bazant M Z, Induced-charge electro-osmosis, JOURNAL OFFLUID MECHANICS 509: 217-252 JUN. 25, 2004

27. J. Voldman, M. Toner, M. L. Gray, and M. A. Schmidt, Design andanalysis of extruded quadrupolar dielectrophoretic traps, Journal ofElectrostatics 57 (2003) 69-90

Process Chart

FIG. 8 illustrates a process chart in accordance with the presentinvention.

Box 800 illustrates forming at least one recurrent circulating fluidflow within the fluid.

Box 802 illustrates introducing at least one particle motivating forceto the fluid having the recurrent circulating fluid flow.

Box 804 illustrates manipulating the at least one particle motivatingforce using electrokinetic properties, the particle motivating forcecomprising at least applied electric fields, wherein the fluidicsolution comprises a total volume of fluid on the order of microliters.

CONCLUSION

In this invention, we claim a device composed of two parts. One partcontaining electrodes used to manipulate solutions. The electrodes canbe embedded on vessels or on a plate. This part can be disposable. Theother part is used to connect the electrodes of the vessels. This secondpart is used to interface an external controller (which sends signals tothe electrodes embedded in the vessels) to the electrodes in order tomanipulate the said fluids or complex solutions. Part of the device hasbuilt in electrodes that can be used to manipulate fluids or solutionsby creating electric fields. Once an electric field is applied,electrokinetic effects are generated.

In this invention, we claim a method to manipulate fluids or fluidicsolutions by creating electric fields with electrodes in direct orindirect contact with fluids or fluidic solutions.

In this invention, we claim a process to manipulate fluids or fluidicsolutions by creating electric fields with electrodes in direct orindirect contact with fluids or fluidic solutions. The process impliesto bring one or more fluids or fluidic solutions in contact withelectrodes. The electrodes are energized, and a force is transmitted tothe fluids.

A device for manipulating fluidic solutions in accordance with thepresent invention comprises a vessel for containing a fluidic solution,and a plurality of electrodes, coupled to the vessel, the plurality ofelectrodes being arranged in an array and each applying an electricfield to the fluidic solution, wherein the plurality of electrodesmanipulate at least one of a flow of the fluidic solution and aseparation of particles in the fluidic solution, the manipulation usingelectrokinetic properties resulting from the applied electric fields,wherein the fluidic solution comprises a total volume of fluid on theorder of microliters.

Such a device further optionally comprises the electrokinetic propertyis at least one of electrothermal convection and electroosmosis, atleast a first electrode in the plurality of electrodes being made from afirst material and at least a second electrode in the plurality ofelectrodes being made from a second material, the array being a periodicarray, each electrode in the periodic array being controlledindependently, at least a first electrode in the plurality of electrodeshaving a first shape and at least a second electrode in the plurality ofelectrodes having a second shape, and the electric field inducing atime-dependent electrohydrodynamic fluid flow.

A method in accordance with the present invention comprises forming atleast one recurrent circulating fluid flow within the fluid, introducingat least one particle motivating force to the fluid having the recurrentcirculating fluid flow, and manipulating the at least one particlemotivating force using electrokinetic properties, the particlemotivating force comprising at least applied electric fields, whereinthe fluidic solution comprises a total volume of fluid on the order ofmicroliters.

Such a method further optionally comprises at least one particlemotivating force directionally interacting with the at least onerecurrent circulating fluid flow in a tangential orientation relative tothe recurrent circulating fluid flow, the at least one particlemotivating force directionally interacting in a tangential orientationat a periphery of the at least one recurrent circulating fluid flow,collecting the particles, and applying a time-dependentelectrohydrodynamic fluid flow.

Another device in accordance with the present invention comprises avessel for containing the fluid to be mixed, a plurality of electrodes,inside the vessel, and a plurality of connectors, coupled to theplurality of electrodes, the plurality of connectors being electricallycoupled to a plurality of applied electric fields, wherein the pluralityof electric fields electrically excite the electrodes thereby creating aflow within the fluid.

Such a device further optionally comprises the plurality of electricfields generating at least one of electrothermal convection andelectroosmosis within the fluid, at least a first electrode in theplurality of electrodes being made from a first material and at least asecond electrode in the plurality of electrodes being made from a secondmaterial, the plurality of electrodes being arranged in a periodicarray, each electrode in the periodic array being controlledindependently, at least a first electrode in the plurality of electrodeshaving a first shape and at least a second electrode in the plurality ofelectrodes having a second shape, and the electric field inducing atime-dependent electrohydrodynamic fluid flow.

This concludes the description of the preferred embodiment of thepresent invention. The foregoing description of one or more embodimentsof the invention has been presented for the purposes of illustration anddescription. It is not intended to be exhaustive or to limit theinvention to the precise form disclosed. Many modifications andvariations are possible in light of the above teaching. It is intendedthat the scope of the invention be limited not by this detaileddescription, but rather by the claims appended hereto and the full rangeof equivalents of the claims appended hereto.

1. A device for manipulating fluidic solutions, comprising: a vessel forcontaining a fluidic solution; and a plurality of electrodes, coupled tothe vessel, the plurality of electrodes being arranged in an array andeach applying an electric field to the fluidic solution, wherein theplurality of electrodes manipulate at least one of: a flow of thefluidic solution, and a separation of particles in the fluidic solution,the manipulation using electrokinetic properties resulting from theapplied electric fields, wherein the fluidic solution comprises a totalvolume of fluid on the order of microliters.
 2. The device of claim 1,wherein the electrokinetic property is at least one of electrothermalconvection and electroosmosis.
 3. The device of claim 2, wherein atleast a first electrode in the plurality of electrodes is made from afirst material and at least a second electrode in the plurality ofelectrodes is made from a second material.
 4. The device of claim 2,wherein the array is a periodic array.
 5. The device of claim 4, whereineach electrode in the periodic array is controlled independently.
 6. Thedevice of claim 2, wherein at least a first electrode in the pluralityof electrodes has a first shape and at least a second electrode in theplurality of electrodes has a second shape.
 7. The device of claim 1,wherein the electric field induces a time-dependent electrohydrodynamicfluid flow. 8-12. (canceled)
 13. A device for mixing a fluid,comprising: a vessel for containing the fluid to be mixed; a pluralityof electrodes, inside the vessel; a plurality of connectors, coupled tothe plurality of electrodes, the plurality of connectors beingelectrically coupled to a plurality of applied electric fields, whereinthe plurality of electric fields electrically excite the electrodesthereby creating a flow within the fluid.
 14. The device of claim 13,wherein the plurality of electric fields generates at least one ofelectrothermal convection and electroosmosis within the fluid.
 15. Thedevice of claim 14, wherein at least a first electrode in the pluralityof electrodes is made from a first material and at least a secondelectrode in the plurality of electrodes is made from a second material.16. The device of claim 14, wherein the plurality of electrodes arearranged in a periodic array.
 17. The device of claim 16, wherein eachelectrode in the periodic array is controlled independently.
 18. Thedevice of claim 14, wherein at least a first electrode in the pluralityof electrodes has a first shape and at least a second electrode in theplurality of electrodes has a second shape.
 19. The device of claim 13,wherein the electric field induces a time-dependent electrohydrodynamicfluid flow.
 20. The device of claim 1, wherein the fluidic solution,when contained in each vessel, comprises a total volume of fluid on theorder of microliters in each vessel.
 21. The device of claim 13, whereinthe fluidic solution, when contained in each vessel, comprises a totalvolume of fluid on the order of microliters in each vessel.
 22. Thedevice of claim 1, wherein said plurality of electrodes are connected toa plate, said plate being attachable and removable from said pluralityof vessels to permit access for adding and removing fluid to saidplurality of vessels.
 23. The device of claim 22, wherein said platecomprises electrical pathways to selectively adder each of saidplurality of electrodes.